Failure to examine the role of chemical messengers other than interstitial cell stimulating hormone (ICSH) led to a narrow view of the control of androgen secretion by mammalian testes. According to this view alterations in testosterone secretion are mediated by ICSH with testosterone acting upon the hypothalamo-hypophyseal complex to regulate ICSH release. This view while correct is too simplistic to explain the total regulation of mammalian testicular androgen secretion. Our rationale for rejecting this simplistic attitude follows: we believe that several chemical messengers act singularly or in concert in a permissive, inductive or inhibitory fashion directly upon the testis to alter androgen biosynthesis and subsequent secretion. Alternatively, the rate of androgen secretion may depend in part upon the rate at which testosterone is metabolized to reduced androstane products in the testis-epididymis prior to its escape into the general circulation. Elucidation of such a complex system controlling androgen secretion escaped notice because of the lack of a suitable testicular preparation facilitating experiments designed to investigate these regulatory mechanisms under controlled conditions. The continued development of the isolated rabbit testis-epididymis perfused with artificial media suggests that this system may be the most realistic one to completely examine the control of androgen secretion by a mammalian testis-epididymis. We will demonstrate that perfused rabbit testes-epididymides secrete testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 Beta- diol and 5 alpha-androstane-3Beta, 17Beta-diol. Moreover we will prove whether or not the 5 alpha reduce compounds are derived from the metabolism of testosterone. We will initiate experiments aimed at demonstrating the site of and mechanism by which FSH stimulates testosterone secretion.